Isolated massive histiocytes renal interstitial infiltration: a case report of an unexpected cause of acute kidney injury in a kidney transplant recipient.

BACKGROUND: Acute kidney injury is a frequent cause of hospital readmission in kidney transplant recipients (KTR), usually associated with infections and graft rejection. Herein, we report a case of an unusual cause of acute kidney injury in a KTR (massive histiocytes renal interstitial infiltration). CASE PRESENTATION: A 40-year-old woman was submitted to a second kidney transplant. One year after surgery, she presented asthenia, myalgia, and fever, haemoglobin 6.1 g/dL; neutrophils: 1.3 × 109/µL; platelets: 143 × 109/µL; blood creatinine 11.8 mg/dL, requiring dialysis. A kidney biopsy revealed diffuse histiocytic infiltration, which was assumed due to dysregulated immunological activation triggered by infections. The patient had multiple infections, including cytomegalovirus infection (CMV), aspergillosis, bacteraemia, and urinary tract infections, which could trigger the immune response. Haemophagocytic lymphohistiocytosis (HLH) was ruled out. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies. CONCLUSIONS: Renal histiocyte activation and infiltration may have been initiated by an immunological mechanism similar to what occurs in HLH and infectious processes. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies.

Management of chronic kidney disease: perspectives of Brazilian primary care physicians.

AIM: To investigate primary care physicians' knowledge of and attitudes toward care for chronic kidney disease patients. BACKGROUND: In Brazil, care for chronic kidney disease, a global public health problem, is provided by the Brazilian National Health System, which is organized around primary care. The study aimed to investigate the knowledge and attitudes of primary care physicians about the management of chronic kidney disease. METHOD: This research is based on quantitative and qualitative data. The participants were 92 physicians from 81 primary care units located in eight cities of the São Paulo/Brazil health region, who answered a self-administered questionnaire. FINDINGS: Only 59% and 58% of the physicians recognized smoking and obesity, respectively, as risk factors for chronic kidney disease. Health appointments and drug therapy predominated as disease prevention strategies and less than 30% mentioned multiprofessional care and health education groups. For early diagnosis, isolated serum creatinine was the most used test and 64.6% stated they classified the disease stages. Exclusive follow-up in primary care decreased from 79% in stage 1 to 19.5% in stage 3B and the patients' monitoring in the healthcare network varied from 8.7% in stage 1 to 70.6% in stages 4 and 5ND, suggesting early referrals and lack of referral at the necessary stages. Access to information on the referred patient was, predominantly, through the patient's report and 74% of the physicians did not have matrix support regarding chronic kidney disease. CONCLUSION: The study showed that the healthcare teams need to update their knowledge and procedures to be able to provide a comprehensive and efficient approach to treating chronic kidney disease in primary care.

Analysis of the role of thyroidectomy and thymectomy in the surgical treatment of secondary hyperparathyroidism.

PURPOSE: Parathyroidectomy can be subtotal or total with an autograft for the treatment of renal hyperparathyroidism. In both cases, it may be extended with bilateral thymectomy and total or partial thyroidectomy. Thymectomy may be recommended in combination with parathyroidectomy in order to prevent mediastinal recurrence. Also, the occurrence of thyroid disease observed in patients with hyperparathyroidism is poorly understood and the incidence of cancer is controversial. The aim of the present study was to report the experience of a single center in the surgical treatment of renal hyperparathyroidism and to analyse the role of thyroid and thymus surgery in association with parathyroidectomy. MATERIALS AND METHODS: We analysed parathyroid surgery data, considering patient demographics, such as age and gender, and surgical procedure data, such as type of hyperparathyroidism, associated thyroid or thymus surgery, surgical duration and mediastinal recurrence. Histopathological results of thyroid and thymus samples were also analysed. RESULTS: Medical records of 109 patients who underwent parathyroidectomy for secondary hyperparathyroidism were reviewed. On average, thymectomy did not have impact on time of parathyroidectomy (p = 0.62) even when thyroidectomy was included (p = 0.91). Intrathymic parathyroids were detected in 7.5% of the thymuses removed and papillary carcinoma was detected in 20,8% of thyroid tissue samples. Two patients showed recurrence of supernumerary intrathymic parathyroids and a single case of mediastinitis was observed. CONCLUSIONS: Parathyroidectomy with thymectomy and/or thyroidectomy has an important role in the treatment of renal hyperparathyroidism since thyroid cancer can frequently occur and require surgery. Thymectomy should be considered to avoid recurrence and a risky re-operation.

Urinary monocyte chemoattractant protein-1 levels and interstitial changes in the renal cortex and their relationship with loss of renal function in renal transplant patients with delayed graft function.

BACKGROUND: Inflammatory cell infiltration and residual areas of fibrosis in kidneys after renal transplantation can lead to functional abnormalities with long-term implications. OBJECTIVES: The aim of this study was to determine urinary monocyte chemoattractant protein-1 (uMCP-1) levels, relative cortical interstitial area (RCIA), and cortical tubulointerstitial macrophage infiltration in renal transplant patients with delayed graft function (DGF) and their possible correlation with graft outcome. DESIGN: Patients were followed after biopsies for one year, and their renal function and structure were evaluated, as well as parameters of inflammatory process. SETTING: Clinical Hospital of the School of Medicine of Ribeirão Preto. PATIENTS: Twenty-two cadaveric kidney transplant recipients with DGF were followed for one year. MEASUREMENTS: Renal function, RCIA, macrophages infiltration and uMCP-1 levels were evaluated. METHODS: Renal function was evaluated by plasma creatinine levels. RCIA was determined by morphometry. Immunohistochemical staining of macrophages was performed using an anti-CD68 monoclonal antibody. uMCP-1 levels were determined using a human MCP-1/CCL2 immunoassay kit. RESULTS: There was a significant increase in uMCP-1 levels in transplant patients compared with controls (p < 0.001). RCIA was 7.1% (6.4 to 9.2; median and 25th to 75th percentiles) in controls and 37.1% (28.1 to 43.7) in patients with kidney transplants (p < 0.001). The patients who presented with a higher RCIA in the first biopsy showed higher levels of plasma creatinine one year after transplantation (r = 0.44; p < 0.05). The number of tubulointerstitial macrophages per 0.10 mm(2) grid field was higher in the renal cortex of transplant patients compared with the controls (19.4 (9.0 to 47.1) vs. 2.5 (1.8 to 3.4), p < 0.001). There was also a positive correlation between the RCIA and the number of tubulointerstitial macrophages in the renal cortex of these patients (r = 0.49; p < 0.001). LIMITATIONS: The number of patients studied was relatively small and may not be reflecting outcomes over a larger spectrum of kidney cadaveric transplants. CONCLUSIONS: Our results demonstrate increased levels of uMCP-1 in transplant patients with DGF, in addition to increased tubulointerstitial macrophage infiltration and RCIA, which could predict the outcome of renal function in these patients.

CONTEXTE: L'infiltration de cellules inflammatoires et la présence de zone de fibrose résiduelle, après la transplantation rénale, peuvent entraîner des anomalies fonctionnelles ayant des incidences à long-terme. OBJECTIFS: Le but de cette étude était de déterminer, chez les patients transplantés avec retard de fonctionnement du greffon (RFG), les taux urinaires de protéine chimiotactique monocytaire-1 (uMCP-1), la zone relative de l'interstitium cortical, et l'infiltration tubulo-interstitielle de macrophages dans le cortex rénal afin d'évaluer la possible corrélation de ses informations et de l'évolution de la transplantation. TYPE D'ÉTUDE: Les patients ont été suivis pendant un an, après biopsie, avec évaluations stucturelle et fonctionnelle, et évaluation des paramètres du processus inflammatoire. CONTEXTE: Hôpital clinique de l'école de médecine de Ribeirão Preto. PATIENTS: Vingt-deux patients ayant reçu un greffon rénal cadavérique avec RFG ont été suivis pendant un an. MESURES: La fonction rénale, l'infiltration de macrophages et les taux d'uMCP-1 ont été évalués. MÉTHODES: La fonction rénale a été évaluée en utilisant les concentrations sériques de créatinine. Une coloration immunohistochimique des macrophages par anticorps monoclonal anti-CD68 a été effectuée. Les concentrations d'uMCP-1 ont été déterminées en utilisant les tests immunologiques de MCP-1/CCL2 humaine. RÉSULTATS: Les concentrations d'uMCP-1 étaient significativement plus élevées chez les patients transplantés que chez les sujets du groupe témoin (p < 0.001). Les médianes de la zone relative de l'interstitium cortical étaient de 7,1% (25ème au 75ème percentiles : de 6,4% à 9,2%) pour le groupe témoin et de 37,1% (de 28,1% à 43,7%) chez les patients transplantés rénaux (p < 0.001). Les patients ayant une la zone relative de l'interstitium cortical plus grande au moment de la première biopsie présentaient une concentration plasmatique de créatinine plus grande un an après la transplantation (r = 0.44; p < 0.05). Le nombre de macrophages dans l'espace tubulo-interstitiel, par champs de 0,10 mm2, était plus élevé dans le cortex rénal des patients transplantés que chez le groupe témoin (19,4 (de 9.0 à 47.1) et 2,5 (de 1.8 à 3,4), p < 0.001). Il existait également une corrélation positive entre la zone relative de l'interstitium cortical et le nombre de macrophages dans l'espace tubulo-interstitiel du cortex rénal de ces patients (r = 0.49; p < 0.001). LIMITES DE L'ÉTUDE: l'échantillon étudié était relativement petit et ne représente pas nécessairement les résultats d'un échantillon plus vaste constitué de patients transplantés avec greffon rénal cadavérique. CONCLUSIONS: Nos résultats démontrent des concentrations d'uMCP-1 plus élevées chez les patients avec RFG, accompagnées d'une infiltration de macrophages dans l'espace tubulo-interstitiel et d'une zone relative de l'interstitium cortical plus grandes, faits qui pourraient prédire l'évolution de la fonction rénale chez ces patients.

Membranous glomerulonephritis associated with splenic marginal zone lymphoma mimicking multiple myeloma.

Glomerulonephritis may complicate the course of a wide variety of malignant diseases. However, there are relatively few reports of membranous glomerulonephritis (MGN) in patients with non-Hodgkin lymphoma (NHL). We describe for the first time a case of MGN associated with splenic marginal zone lymphoma with extreme plasmacytic differentiation and bone marrow infiltration mimicking multiple myeloma. We also reviewed the literature and summarize the clinical-pathological findings and the mechanisms involved in NHL-induced MGN. Our current case highlights the importance of a quick and correct diagnosis of the underlying disease and the value of a thorough physical examination. Clinicians should be aware of the possibility of an underlying hematologic malignancy in such cases, particularly in elderly patients with renal biopsy that shows the presence of atypical histology.

What lies beneath: Fabry nephropathy in a female patient with severe cerebrovascular disease.

Fabry disease is an X-linked inborn error of metabolism, which is caused by the deficiency of α-galactosidase A, leading to progressive accumulation of neutral glycosphingolipids and a-galactosyl breakdown products in most body fluids and several tissues, resulting in the clinical manifestations. The onset of Fabry disease symptoms in females is not observed as early as in males. We report a novel presentation of Fabry disease in a female patient with medical history of relapsing strokes and brain magnetic resonance angiography showing signs of microangiopathy and multiple lacunar strokes that were first diagnosed as Moyamoya disease (a chronic progressive cerebrovascular disease). The patient subsequently displayed increased levels of serum creatinine and proteinuria. Diagnosis of Fabry disease was made by a renal biopsy and was confirmed by molecular studies showing a missense mutation: c1066C > T (het) [R356W]. The diagnosis was delayed by 21 years with respect to her first symptom (stroke), probably because her initial clinical presentation was neurological and diagnosed as Moyamoya disease. Other factors that contributed to the delay of the diagnosis were the lack of acute or chronic pain (neuropathic pain) and angiokeratomas. Some similarities in the pathogenic aspects of the patient's vascular lesions lead us to speculate that this patient has Fabry disease, with a phenotype that had not yet been described. It is necessary to be aware of this possibility to avoid misdiagnosis of Fabry disease as Moyamoya disease.

Minimal change disease associated with type 1 and type 2 diabetes mellitus.

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents.

Minimal change disease associated with type 1 and type 2 diabetes mellitus / Glomerulopatia de lesões mínimas associada ao diabetes melito do tipo 1 e do tipo 2

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents.

Uma paciente de 19 anos de idade com diabetes tipo 1 durante quatro anos e uma paciente de 73 anos de idade com diabetes tipo 2 durante vinte anos desenvolveram quadro súbito de síndrome nefrótica. O exame histológico à microscopia de luz, imunofluorescência e microscopia eletrônica (em um caso) diagnosticou glomerulopatia de lesões mínimas (GLM) em ambos os casos. Na paciente de 73 anos de idade, houve uma associação com o uso de meloxicam. As duas pacientes foram tratadas com corticosteroides e responderam com remissão completa do quadro. A paciente de 19 anos com diabetes tipo 1 apresentou remissão completa sem recidivas, e a paciente de 73 anos com diabetes tipo 2 apresentou dois episódios de recidiva; a remissão completa foi conseguida após associação ao tratamento com ciclofosfamida. As duas pacientes foram seguidas dois anos após a remissão completa. Os casos descritos enfatizam o papel da biópsia renal em pacientes diabéticos com evolução atípica do aparecimento de proteinúria, pois pacientes com GLM respondem bem à corticoterapia como único tratamento ou associado a outro agente imunossupressor.

Minimal change disease: a variant of lupus nephritis.

Some patients with systemic lupus erythematosus (SLE) present with nephrotic syndrome due to minimal change disease (MCD). Histopathological diagnosis of patients with SLE and nephrotic-range proteinuria has shown that these patients present with diffuse proliferative glomerulonephritis and membranous glomerulonephritis, World Health Organization (WHO) classes IV and V, respectively, more frequently than the other classes. In the present study, we reported a case of nephrotic syndrome and renal biopsy-proven MCD associated with SLE. A complete remission occurred after steroid treatment, which was followed by a relapse 15 months later with a concomitant reactivation of SLE. A second biopsy showed WHO class IIb lupus nephritis. Prednisone treatment was restarted, and the patient went into complete remission again. The association of MCD and SLE may not be a coincidence, and MCD should be considered as an associated SLE nephropathy.